Rocuronium bromide is a steroidal non-depolarizing muscle relaxant developed by a Dutch company Organon, and was firstly marketed in the US in 1994. This drug is currently the most widely used muscle relaxant internationally, and in North America and most European countries, the consumption thereof is the highest among all the muscle relaxants. Rocuronium bromide is a novel mono-quaternary ammonium muscle relaxant, and is used as an anaesthetic adjuvant for endotracheal intubation under anesthesia and muscle relaxation during surgery, and is the non-depolarizing muscle relaxant having the shortest onset time in clinical use. It is characterized in the quick onset of action, rapid recovery, week inhibition to the cardiovascular system, and having no effect of histamine release. Rocuronium bromide has the following chemical structural formula:

European patent EP0287150 firstly discloses a process for preparing rocuronium bromide, wherein rocuronium bromide is obtained by subjecting 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α-ol, 17β-acetate (hereafter referred to as Rocu 8) and 3-bromopropylene to a quaternization reaction, and the reaction equation thereof is as follows:

After completion of the reaction, the reaction liquid is evaporated to dryness, the product is dissolved in dichloromethane, and the resultant solution is added to diethyl ether to collect and obtain rocuronium bromide. The rocuronium bromide obtained from this method has very high content of residual solvent, and it is found by experiments that the content of residual solvent can be up to 16%, and the residual 3-bromopropylene is up to approximately 400 ppm.
In addition, the ester group in 17-position of the structure of rocuronium bromide will be hydrolyzed to form a hydrolyzed impurity (impurity C in USP pharmacopeia), which is formed by reaction of the incompletely reacted material of the reactant Rocu 8 in the previous step with 3-bromopropylene, and the simultaneous hydrolysis reaction occurring during post-processing of rocuronium bromide or with the water contained in itself. It is the main impurity which needs to be controlled in formulation product, and has the following chemical structural formula:

Furthermore, the impurity generated by decomposition of the incompletely reacted Rocu 8 and decomposition of rocuronium bromide during post-processing and storage (impurity A in USP pharmacopeia) is also the main impurity which needs to be controlled in formulation product, and has the following chemical structural formula:

Moreover, it is reported that lower halohydrocarbons have genotoxicity, and generally the toxicity decreases in the order of bromohydrocarbons, chlorohydrocarbons, and fluorohydrocarbons. Consequently, the raw material 3-bromopropylene used in synthesis of rocuronium bromide is also a potential substance having genotoxicity.
US patent US2006058275 discloses a method for lyophilizing rocuronium bromide, wherein a buffer solution comprising acetic acid and sodium acetate is added during the lyophilization. Since water and acetic acid in the buffer system tend to decrease as the lyophilization goes on, the PH value during lyophilization is unstable, the final product is severely decomposed, and the resultant product is not a single, pure rocuronium bromide. British patent GB2445746 mentions a process for lyophilizing a aqueous solution of rocuronium bromide: rocuronium bromide is dissolved in an aqueous solution with a PH of lower than 4˜5 (adjusting the PH value with carbon dioxide), then carbon dioxide is employed to adjust the PH to 8 or lower, the solution is then concentrated and detected for the amount of residual solvents, and then lyophilization is carried out. This process is tedious in operation, and the amount of residual 3-bromopropylene in the resultant product is more than 100 ppm. Therefore, it is of great significance to develop a method for preparing rocuronium bromide with high purity.